DSC-FTIR microspectroscopy used to investigate the heat-induced intramolecular cyclic anhydride formation between Eudragit E and PVA copolymer

INTRODUCTION Acrylic resins containing acrylic acid (AA), methyl methacrylate (MMA) or acrylic–methacrylic copolymer are the most commonly used polymeric materials for biomedical and pharmaceutical applications owing to their hydrophilicity and biocompatibility.1–4 Recently, a new polyvinyl alcohol (PVA) copolymer designed by copolymerizing AA and MMA with PVA was successfully developed as a capsule shell for filling liquid formulations to enhance the bioavailability of waterinsoluble drugs.5–7 PVA was used as a skeleton in the structure of PVA copolymer; MMA and AA were separately copolymerized to increase the hardness of the capsule shell and the solubility in water. Furthermore, the PVA copolymer has also been reported to act as a binder or film-coating agent in pharmaceutical applications.8–10 In particular, the oxygen-blocking and light-protective properties of PVA copolymer film have increased its usage in the pharmaceutical industry.9,10 The stability of PVA copolymer is another important factor for pharmaceutical applications. Because the stability of PVA copolymer may significantly influence the physico-chemical properties and efficacy of a drug after application of PVA copolymer, accelerated stability tests for PVA copolymer should be performed to predict the storage stability and quality of drug products. Accelerated stress conditions, including heat, humidity and light, have become a popular parameter for evaluating the reliability of drug products within short testing periods.11,12 Our previous study provided the first evidence of thermally induced anhydride formation in Eudragit E, a copolymer composed of butyl methacrylate, 2-dimethylaminoethyl methacrylate and MMA in the composition 1:2:1.13 PVA copolymer has also been copolymerized by AA and MAA with PVA,5–7 but the thermal stability has not yet been investigated. In the present study, a highly specialized and powerful Fourier transform infrared (FTIR) microspectroscopy equipped with a differential scanning calorimeter (DSC) was used to examine the thermal stability of PVA copolymer. Eudragit E was used for comparison. EXPERIMENTAL PROCEDURE Materials PVA copolymer (POVACOAT, Type F, Mw: 40 000) and Eudragit E 100 (Mw: 150 000) were kindly supplied by Nissin Kasei (Osaka, Japan) and Evonik Industries AG (Essen, Germany), respectively. Reagent-grade anhydrous ethanol (99.9%) and KBr cubic crystal (5 5 5 mm3) were purchased from Nakalai Tesque (Kyoto, Japan) and Jasco (Tokyo, Japan).